Chemotherapy as a single modality

There is no study that has systematically evaluated the chemotherapy alone for patients with OMBC. Greenberg et al. retrospectively reviewed 1581 MBC patients, mostly chemotherapy naïve, who were treated with anthracycline and alkylating agents based regimens of whom 1293 (82%) had 1-3 metastatic sites.[13] After completion of treatment, 3.1% of all patients remained in CR for more than 5-year of whom 92% had oliogometastatic (1-2 sites) disease at baseline. This suggests a somewhat higher propensity for OMBC to attain long term remissions and functional cures.[13] This study along with others suggests that patients with low tumor burden metastatic disease are likelier to achieve CR, in turn implying that long term survival was related to low tumor burden/OMBC.[14] It remains unclear whether long term survival is due to chemotherapy or favorable disease biology or their interaction. A randomized trial addressing this issue will be difficult to implement because of obvious reasons.

High-dose chemotherapy for oligometastatic breast cancer

High-dose chemotherapy (HDCT) followed by autologous peripheral blood progenitor cell rescue has been compared with conventional chemotherapy in patients with MBC in many trials, but the approach remains controversial. The Cochrane review included six randomized controlled trials (RCTs) demonstrating a significantly improved event-free survival (EFS) at 3, 4, and 5 years after treatment with HDCT, but no overall survival (OS) benefit.[15] Similarly, a recent meta-analysis of 15 trials that included data on 6210 patients showed significant EFS benefit but none in OS, in favor of HDCT.[16]

Data for OMBC treated with HDCT is sparse. Nieto et al. reported a prospective study of 60 OMBC patients who received induction chemotherapy followed by local treatment followed by hematopoietic stem cell transplantation (HSCT).[17] The 5-year relapse free survival was 52% in this population. Bojko et al., in a similar small prospective study involving OMBC patients treated with induction chemotherapy followed by local treatment followed by HSCT, reported a 5-year progression free survival (PFS) of 27%.[18] The difference in outcomes between the two preceding studies could be explained by inclusion of patients with liver metastases (29%) in the second study. Although the results are encouraging, based on these small nonrandomized studies no recommendations can be made regarding the use of HSCT in OMBC patients. Future studies should aim at evaluating the molecular characteristics of patients who may benefit from this treatment.

Surgery of the primary site in oligometastatic breast cancer

The potential advantages of removing the primary tumor in OMBC is elimination of a potential source of further metastatic seeding, restoration of immune competence and reduction in chemoresistance by reducing the number of clones.[19] Arguments against removal of the primary tumor include Fisher's mouse experimental model which suggested increase in the proliferation of distant tumor foci (“metastasis”) associated with the removal of primary tumor masses in different tumor types.[20]

Until recently there were several retrospective series that showed benefit of local treatment of the primary tumor but these studies included selected patients with better performance status, less advanced primary tumor and lower disease burden. It is difficult to ascribe the outcomes to local treatment versus disease biology in these reports.[21]

Badwe et al. conducted a RCT to address this issue.[22] In the overall study population (N = 350) of patients with MBC who were responding to anthracycline based chemotherapy, they found no benefit of loco-regional therapy (LRT) in terms of OS. In a preplanned subset of patients with oligometastatic (≤3) disease there was no difference in OS between the LRT and no LRT arms. Until the presentation of further randomized results, this remains the best evidence on this question and routine surgery for the primary tumor cannot be recommended in OMBC.

Role of surgery/local therapy of metastatic sites

Again, there is sparse evidence for metastatectomy in patients with OMBC. The largest retrospective data comes from International Registry of Lung Metastasis, which was established in 1991 to collect the experience of curative intent surgery for pulmonary metastases. Among breast cancer patients (N = 467) who underwent metastatectomy, the median survival was 35 months with 15-year survival of 18%.[23] Being retrospective and nonrandomized this data suffers from the same biases that were earlier pointed out for local therapy in such cases.[19] Although evidence remains inconclusive about its therapeutic value, pulmonary metastatectomy does have a useful role in the confirmation of diagnosis in some patients. Rena et al. evaluated a series of 79 consecutive patients who underwent surgery for solitary pulmonary nodule after a curative resection for breast cancer.[24] Histopathological evaluation of the resected specimen revealed primary lung cancer in 38 patients, pulmonary metastasis from breast cancer in 27 and benign conditions in 14.

Unlike pulmonary resection, liver resection is practiced less often but multiple retrospective analyses in highly selected group of patients show favorable long term survival. Other techniques of local control like sterotactic body radiotherapy and radiofrequency ablation are being increasingly used, but their role is not yet clear.[11,19]

Thus, metastatectomy in OMBC for therapeutic benefit is not considered standard of care but may be undertaken in individual cases especially to rule out other diagnoses.[25]